AP1B1 p.Ala783Ala

Variant names:

• chr22-29331876-G-G
• NM_001127.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr22-29331877--
• chr22-29331877-C-A
• chr22-29331877-C-G
• chr22-29331877-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001127.4(AP1B1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP1B1 NM_001127.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.15
• Publications: 0 publications found

Genes affected

AP1B1 (HGNC:554): (adaptor related protein complex 1 subunit beta 1) Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large, one medium, and one small adaptin subunit. The protein encoded by this gene serves as one of the large subunits of this complex and is a member of the adaptin protein family. This gene is a candidate meningioma gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

AP1B1 Gene-Disease associations (from GenCC):

• ichthyosiform erythroderma, corneal involvement, and hearing loss

  Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, G2P, ClinGen
• MEDNIK syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1B1	NM_001127.4	MANE Select	c.		exon_region	Exon 18 of 23	NP_001118.3
	AP1B1	NM_001378562.1		c.		exon_region	Exon 18 of 22	NP_001365491.1
	AP1B1	NM_001378563.1		c.		exon_region	Exon 17 of 22	NP_001365492.1	Q10567-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1B1	ENST00000357586.7	TSL:1 MANE Select	c.		exon_region	Exon 18 of 23	ENSP00000350199.2	Q10567-1
	AP1B1	ENST00000317368.11	TSL:1	c.		exon_region	Exon 17 of 21	ENSP00000319361.7	Q10567-4
	AP1B1	ENST00000482818.1	TSL:1	n.		exon_region	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-29727865;